Tabebordbar, MohammadsharifZhu, KexianCheng, Jason K. W.Chew, Wei LeongWidrick, JeffreyYan, WinstonMaesner, ClaireWu, Elizabeth Y.Xiao, RuRan, F. AnnCong, LeZhang, FengVandenberghe, LukChurch, GeorgeWagers, Amy2021-10-052016-01-22Tabebordbar, Mohammadsharif, Kexian Zhu, Jason K. W. Cheng, Wei Leong Chew, Jeffrey Widrick, Winston Yan, Claire Maesner et al. "In Vivo Gene Editing in Dystrophic Mouse Muscle and Muscle Stem Cells." Science 351, no. 6271 (2016): 407-411. DOI: 10.1126/science.aad51770036-80751095-9203https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369687Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated but still functional protein. In this study, we develop and test a direct gene editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored Dystrophin reading frame in myofibers, cardiomyocytes and muscle stem cells following local or systemic delivery. AAV-Dmd CRISPR-treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.en-USJournal Article2017-08-0320152021-10-0510.1126/science.aad5177